Park Kyung Min, Gerecht Sharon
Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center, and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
1] Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center, and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA [2] Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Nat Commun. 2014 Jun 9;5:4075. doi: 10.1038/ncomms5075.
Oxygen is vital for the existence of all multicellular organisms, acting as a signalling molecule regulating cellular activities. Specifically, hypoxia, which occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role during development, regeneration and cancer. Here we report a novel hypoxia-inducible (HI) hydrogel composed of gelatin and ferulic acid that can form hydrogel networks via oxygen consumption in a laccase-mediated reaction. Oxygen levels and gradients within the hydrogels can be accurately controlled and precisely predicted. We demonstrate that HI hydrogels guide vascular morphogenesis in vitro via hypoxia-inducible factors activation of matrix metalloproteinases and promote rapid neovascularization from the host tissue during subcutaneous wound healing. The HI hydrogel is a new class of biomaterials that may prove useful in many applications, ranging from fundamental studies of developmental, regenerative and disease processes through the engineering of healthy and diseased tissue models towards the treatment of hypoxia-regulated disorders.
氧气对于所有多细胞生物的生存至关重要，它作为一种调节细胞活动的信号分子发挥作用。具体而言，当氧分压降至5%以下时发生的缺氧，在发育、再生和癌症过程中起着关键作用。在此，我们报告一种由明胶和阿魏酸组成的新型缺氧诱导（HI）水凝胶，其可通过漆酶介导的反应中消耗氧气形成水凝胶网络。水凝胶内的氧气水平和梯度能够被精确控制和准确预测。我们证明，HI水凝胶通过缺氧诱导因子激活基质金属蛋白酶在体外引导血管形态发生，并在皮下伤口愈合过程中促进宿主组织的快速新生血管形成。HI水凝胶是一类新型生物材料，可能在许多应用中证明是有用的，从发育、再生和疾病过程的基础研究，到通过构建健康和患病组织模型来治疗缺氧调节紊乱。
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